title: TDP-43 expression in mouse models of amyotrophic lateral sclerosis and spinal muscular atrophy.
abstract: BACKGROUND
  Redistribution of nuclear TAR DNA binding protein 43 (TDP-43) to the cytoplasm and ubiquitinated inclusions of spinal motor neurons and glial cells is characteristic of amyotrophic lateral sclerosis (ALS) pathology. Recent evidence suggests that TDP-43 pathology is common to sporadic ALS and familial ALS without SOD1 mutation, but not SOD1-related fALS cases. Furthermore, it remains unclear whether TDP-43 abnormalities occur in non-ALS forms of motor neuron disease. Here, we characterise TDP-43 localisation, expression levels and post-translational modifications in mouse models of ALS and spinal muscular atrophy (SMA).
  
  
  RESULTS
  TDP-43 mislocalisation to ubiquitinated inclusions or cytoplasm was notably lacking in anterior horn cells from transgenic mutant SOD1G93A mice. In addition, abnormally phosphorylated or truncated TDP-43 species were not detected in fractionated ALS mouse spinal cord or brain. Despite partial colocalisation of TDP-43 with SMN, depletion of SMN- and coilin-positive Cajal bodies in motor neurons of affected SMA mice did not alter nuclear TDP-43 distribution, expression or biochemistry in spinal cords.
  
  
  CONCLUSIONS
  These results emphasise that TDP-43 pathology characteristic of human sporadic ALS is not a core component of the neurodegenerative mechanisms caused by SOD1 mutation or SMN deficiency in mouse models of ALS and SMA, respectively.
authors.affiliation: University of Oxford, MRC Functional Genetics Unit, Department of Physiology, Anatomy and Genetics, South Parks Road, Oxford, OX1 3QX, UK. bradley.turner@florey.edu.au
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Turner
authors.forename: Dirk
authors.initials: D
authors.lastname: Bäumer
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Parkinson
authors.forename: Jakub
authors.initials: J
authors.lastname: Scaber
authors.forename: Olaf
authors.initials: O
authors.lastname: Ansorge
authors.forename: Kevin
authors.initials: K
authors.lastname: Talbot
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000870:Anterior Horn Cells / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D020541:Coiled Bodies / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009134:Muscular Atrophy, Spinal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011499:Protein Processing, Post-Translational / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics; D054875:Ubiquitination
chemical_list: D004268:DNA-Binding Proteins; D055533:Survival of Motor Neuron 1 Protein; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase